OBJECTIVE: The purpose of this investigation is to evaluate the neurophysiological and neuropharmacological changes produced in the central nervous system by capsaicin (a homovanillylamide derivative and the pungent principle in red pepper) and to explore the potential uses of this compound or its analogs in the identification and functional evaluation of neurotransmission involving the polypeptide, substance P. Microphysiological techniques would be used to detect changes in the activity of single neurones in response to physiologically or electrically evoked synaptic activity and to determine changes in drug and neurotransmitter sensitivity of these cells following capsaicin. Two central areas would be explored, dorsal horn neurons in the cat spinal cord and supra-spinal neurons in the rat substantia nigra. Cells would be physiologically identified in the spinal cord following stimulation of their peripheral receptive fields, those responding to both noxious and innocuous stimuli would be selected. Experiments in the basal ganglia would involve electrical stimulation of the stratium and the recording of synaptic activity in the ipsilateral substantia nigra. Neurones in both areas would be tested with microelectrophoretically administered substance P, other neurotransmitters and opiate drugs. The synaptic inffuences of midbrain raphe stimulation on neurones in both areas would be tested. These studies would provide additional information concerning adaptive changes in the CNS following the selective removal of substance P, the involvement of analgesic actions of opiate drugs with in vivo substance P neurotransmission and explore the potential use of capsaicin in treatment and etiology of neurological disease.